Multilevel analyses of SCN5A mutations in arrhythmogenic right ventricular dysplasia/cardiomyopathy suggest non-canonical mechanisms for disease pathogenesis

Abstract

Almost 2% of ARVD/C patients harbour rare SCN5A variants. For one of these variants, we demonstrated reduced sodium current, Na_v1.5 and N-Cadherin clusters at junctional sites. This suggests that Na_v1.5 is in a functional complex with adhesion molecules, and reveals potential non-canonical mechanisms by which Na_v1.5 dysfunction causes cardiomyopathy.